Safety and Efficacy of HSK3486 Compared to Propofol for Induction of General Anesthesia in Adults With Elective Surgery

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Haisco-USA Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

Trial duration

8 May 2024 → 23 Jul 2024

Decision date (initial)

2024-02-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Haisco-USA Pharmaceuticals Inc.

External identifiers

EU CT number

2023-507009-32-00

ClinicalTrials.gov

NCT05486416

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate HSK3486 0.4/0.2 mg/kg (0.4 mg/kg intravenous [IV] slow injection for the first dose, an
additional 0.2 mg/kg if needed) is non-inferior to propofol 2.0/1.0 mg/kg (2.0 mg/kg IV slow injection for first
dose, an additional 1.0 mg/kg if needed) in success of induction of general anesthesia in adults undergoing
elective surgery.

Secondary objectives 2

1. To confirm that HSK3486 0.4/0.2 mg/kg leads to statistically significant less injection-site pain in all compared to propofol 2.0/1.0 mg/kg during the induction of general anesthesia in adults undergoing elective surgery.
2. To demonstrate HSK3486 0.4/0.2 mg/kg provides better anesthetic effects compared to propofol 2.0/1.0 mg/kg without significant cardiac and respiratory depression in conjunction with other routinely used preinduction and maintenance anesthetic agents in the induction of general anesthesia in adults undergoing elective surgery.

Conditions and MedDRA coding

General anaesthesia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Subjects undergoing elective surgery (non emergency, noncardiothoracic, and non intracranial surgery, anticipated to last at least 1 hour) requiring endotracheal intubation and inhalation general anesthesia during the maintenance period. Duration of surgery is defined as time from study drug administration to time of transfer from operating room to recovery room or PACU.
2. Males or females, aged ≥18 years old, with ASA-PS I to IV. For ASA-PS IV subjects, clinical status must be optimized at time of preoperative anesthesia evaluation per judgement of the anesthesiologist.
3. BMI ≥18 kg/m2.
4. Vital signs at screening: RR ≥10 and ≤24 breaths/min; SpO2 ≥92% in ambient air; SBP ≥90 and ≤160 mmHg; DBP ≥55 and ≤100 mmHg; HR ≥55 (or ≥50 if subjects are on beta blockers) and ≤100 beats/min.
5. For all women of childbearing potential, negative serum pregnancy test within the screening period and negative urine pregnancy test at baseline (Day 1). Additionally, women of childbearing potential and male subjects with female partners of childbearing potential must agree to use effective contraception from the time of consent until 30 days post study drug administration.
6. Capable of understanding the procedures and methods of this study, willing to sign an Informed Consent Form, and able to complete this study in strict compliance with the study protocol.
7. Willing to comply with the site’s COVID guidelines and testing requirements as applicable.
8. Patients with psychiatric/mental disorders must be considered stable on treatment (e.g., SSRIs, SNRIs, TCAs, MAOIs, psychotherapy) per investigator judgement, and no hospitalizations and urgent care due to the underlying psychiatric pathology for at least 12 months.
9. For subjects with known hypothyroidism and/or on thyroid-hormone replacement treatment (i.e., thyroxine), or subjects suspected to have thyroid dysfunction based on clinical laboratory and physical exam, a TSH must drawn and be within normal levels.

Exclusion criteria 8

1. Contraindications to deep sedation/general anesthesia or a history of adverse reaction to sedation/general anesthesia.
2. Known to be allergic to eggs, soy products, opioids and their antidotes, or propofol; subjects having contraindications to propofol, opioids, and their antidotes. In cases where the only previous reaction to opioids was itching or nausea, subjects need not be excluded if the investigator believes the subject is not truly allergic to opioids.
3. Medical condition or evidence of increased sedation/general anesthesia risk as follows: a) Cardiovascular disorders: uncontrolled hypertension (SBP >160 mmHg and/or DBP >100 mmHg) with or without antihypertensive therapy (antihypertensive therapy should be stable for 1 month prior to screening), serious arrhythmia (including the subjects with implanted pace makers), unstable heart failure, Adams-Stokes syndrome (i.e., syncope or near syncope due to cardiac arrythmia), unstable angina, myocardial infarction occurring within 6 months prior to screening, history of tachycardia/bradycardia requiring medications, third degree atrioventricular block or QT interval corrected for HR using Fridericia’s formula (QTcF) ≥450ms for males and ≥470ms for females. b) History of severe obstructive lung disease (i.e., forced expiratory volume in 1 second [FEV1] <50% predicted), history of bronchospasm requiring treatment in a hospital emergency room or hospitalization occurring within 3 months prior to screening, developing acute respiratory tract infection within 2 weeks prior to baseline (such as symptoms of fever, shortness of breath, wheezing, nasal congestion, and cough). c) Cerebrovascular disease: subject with a history of serious craniocerebral injury, convulsion, seizure disorder, intracranial hypertension, cerebral aneurysm, or stroke. d) Patients with psychiatric/mental disorders who have not been on a stable treatment regimen (e.g., SSRIs, SNRIs, TCAs, MAOIs, psychotherapy) per investigator judgement, for at least 12 months or who have been hospitalized or had emergent/urgent care due to underlying psychiatric pathology within the last 12 months. e) Uncontrolled clinically significant conditions of liver (e.g., severe hepatic insufficiency defined as Childs- Pugh class C), kidney, gastrointestinal tract, blood system, nervous system, or metabolic system diseases, judged by the investigator to be unsuitable for involvement in the study. f) History of uncontrolled diabetes in the opinion of the investigator. g) History of alcohol abuse within 3 months prior to screening, where alcohol abuse refers to daily alcohol drinking >2 units of alcohol (1 unit = 360 mL of beer or 45 mL of spirit with a strength of 40% or 150 mL of wine). h) History of drug abuse that, in the opinion of the investigator, may confound the interpretation of safety or efficacy in a study subject. i) For subjects with known hypothyroidism and/or on thyroid-hormone replacement treatment (i.e. thyroxine), or subjects suspected to have thyroid disfunction based on clinical laboratory and physical exam who has a TSH value outside the normal range.
4. Management risks of respiratory tract and judged by the investigator to be unsuitable for inclusion in the study as follows: a) Asthma must be stable: stable doses of asthma medications for the past 6 months, no requirement for rescue inhalers or oral steroids within past 6 months, not evaluated in emergency department, urgent care, or hospitalized for an asthma attack within past 1 year. b) History (or family history) of malignant hyperthermia. c) Any previous failure of tracheal intubation. d) Judged to have a difficult airway for endotracheal intubation in the opinion of the Investigator based on parameters such as modified Mallampati score (Grade III or IV), neck mobility, short thyromental distance, and/or history of difficult intubation.
5. Any medication that has the potential to interact synergistically with propofol or HSK3486, including but not limited to all sedatives and hypnotics (e.g., benzodiazepines and opioids) taken within 5 half-lives prior to Day 1.
6. Laboratory parameters measured at screening with the following levels: a) Neutrophil count ≤1.5 x 10^9/L b) Platelet count <80 x 10^9/L c) Hemoglobin <90 g/L (without blood transfusion within 14 days) d) Alanine transaminase and/or aspartate transaminase ≥2.0 x upper limit of normal (ULN) e) Total bilirubin ≥2.0 x ULN f) Severe renal impairment defined by creatinine clearance (CrCl) ≤30 mL/min
7. Female subjects with a positive pregnancy test at screening (serum) or baseline (urine); lactating subjects; any subject planning to get pregnant within 1 month after the study (including the male subject’s partner).
8. Judged by the investigator to have any other factors that make the subject unsuitable for participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Success rate of general anesthesia induction: A successful general anesthesia induction will meet both of the following conditions: a) Induction success (MOAA/S ≤1) after administration of the study drug, and b) One or less top-up doses required without using any rescue drugs.

Secondary endpoints 2

1. The proportion of subjects with any injection-site pain at time of drug administration on the Numeric Rating Scale (NRS ≥1).
2. The proportion of subjects with successful induction who maintain the desired depth of anesthesia for general elective surgery, and without significant cardiac and respiratory depression within 15 minutes post initiation start of study drug administration.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Haisco-USA Pharmaceuticals Inc.

Sponsor organisation

Haisco-USA Pharmaceuticals Inc.

Address

1200 Us Highway 22 Suite 2000

City

Bridgewater

Postcode

08807-2943

Country

United States

Scientific contact point

Organisation

Haisco-USA Pharmaceuticals Inc.

Contact name

Clinical Trial Info

Public contact point

Organisation

Haisco-USA Pharmaceuticals Inc.

Contact name

Clinical Trial Info

Third parties 5

Locations

2 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications